Our work is directed toward establishing the details of the molecular and electronic structure of the copper centers in proteins as well as toward gaining mechanistic insight into the mode of action of these novel redox catalysts. Approaching the problem from the protein side, we are trying to develop specific chemical modification procedures and to combine these studies with precise spectroscopic measurements. Thus, for laccase, a copper-containing oxidase which contains 4 coppers per active unit, we are attempting to prepare hybrid derivatives of the enzyme which have non-redox-active metals replicating some of the copper of the native protein. Comparisons between such derivatives and the native system should lead to insight into the intramolecular electron transfer processes of the enzyme. We are also carrying out inhibitor studies of this enzyme with the goal of defining systems which specifically interact with the type 3 site. At the present the type 3 site is the least well understood of the three basic types of copper sites in proteins. From the synthetic end we are attempting to prepare small molecule analogues of the type 1 and type 3 sites.